Enones, oxidative ozonolysis

Cyclic enones can be oxidatively cleaved by a range of reagents to yield keto acids. As ozonolysis can be quite hazardous for large-scale preparations with the build up of ozonides, the procedure has been modified using quaternary ammonium salts to catalyse the transfer of peroxide anion for a rapid oxidative work-up [32]. Two methods are available but, in the safer procedure (10.7.15.A), there is no effective build-up of the ozonide. 

Known bicyclo[4.3.1]enone 15758 was converted into vinylsilane 158 with bis(trimethylsilyl)methyl lithium.55 Diene 158 underwent selective ozonolysis at the cis-olefin under conditions to produce differentially oxidized termini 90 alde-hydo-ester 159 was homologated with a phosphine oxide anion91 to enol 160. Subsequent hydrolysis of 161 provided substrate 162, which after tandem ozonolysis-acidification gave racemic 6,9-desmethyl analogue 155. Unfortunately, initial efforts failed to resolve 155 into its two optical isomers with cellulose triacetate.92 However, the antimalarial activity of racemate 155 is intriguing, as discussed in a later section. 

This last example makes it clear that we shall normally have to make the cyclohexenes we need for oxidative cleavage and one of the best routes to such compounds is the Diels-Alder reaction (Chapter 17). A generalised example would be ozonolysis of the alkene 21, the adduct of butadiene and the enone 20. The product 22 has a 1,6-relationship between the two carboxylic acids. Since Diels-Alder adducts have a carbonyl group outside the ring (the ketone in 21) the cleavage products 22 also have 1,5- and 1-4-diCO relationships and would be a matter for personal judgement which of these should be disconnected instead if you choose that alternative strategy. 

Swem oxidation, provides enone 476. After reduction of ketone 476 to the ally lie alcohol, ozonolysis and reduction give triol 477, which is oxidatively cleaved to 2,3 4,5-di-0-isopropylidene-L-glucose. On treatment with acid, L-glucose is released [213a]. 

Ozonolysis of solasodine (1) and of the derived enone (8), with oxidative work-up, gave the keto-acids (18) and (19), respectively. These products were characterized as their methyl esters and as the acetates of the products of lithium aluminium hydride reduction of the methyl esters. Ozonolyses of (20) and (21) to give analogous products were also described. The aglycone (22) of the steroidal glycoside osladine has been synthesized from solasodine via the azomethine (23) and ketone (24). ... 

An interesting synthesis of almost pure methyl cis-dihydrojasmonate is provided by Ebert and Krause. [93] The key step is a diastereoselective protonation of an enolate, generated from 2-pentylcyclopent-2-enone and hthium diallylcu-prate. Ozonolysis, oxidation and esterification give methyl dihydrojasmonate, which is 91 % ds configured. 

Dicarbonyl Compounds.—Ozonolysis of 2-cyclopentylidenecyclopentanone provides a convenient synthesis of cyclopentane-l,2-dione on the ca. 0.4 mole scale.The by-product, cyclopentanone, is recycled via an aldol condensation to regenerate the enone. The method should be applicable to other alicyclic 1,2-diones. Various methods for the preparation of monoprotected 1,2-diones have appeared. Monoacetals of a-dicarbonyl compounds are prepared regio-specifically from enol ethers [equation (32)], following epoxidation in methanol and oxidation of the resulting acyloin acetal. 

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